A hierarchical frailty model applied to two-generation melanoma data.

We present a hierarchical frailty model based on distributions derived from non-negative Lévy processes. The model may be applied to data with several levels of dependence, such as family data or other general clusters, and is an alternative to additive frailty models. We present several parametric examples of the model, and properties such as expected values, variance and covariance. The model is applied to a case-cohort sample of age at onset for melanoma from the Swedish Multi-Generation Register, organized in nuclear families of parents and one or two children. We compare the genetic component of the total frailty variance to the common environmental term, and estimate the effect of birth cohort and gender.

Frailty modeling of bimodal age-incidence curves of nasopharyngeal carcinoma in low-risk populations.

The incidence of nasopharyngeal carcinoma (NPC) varies widely according to age at diagnosis, geographic location, and ethnic background. On a global scale, NPC incidence is common among specific populations primarily living in southern and eastern Asia and northern Africa, but in most areas, including almost all western countries, it remains a relatively uncommon malignancy. Specific to these low-risk populations is a general observation of possible bimodality in the observed age-incidence curves. We have developed a multiplicative frailty model that allows for the demonstrated points of inflection at ages 15-24 and 65-74. The bimodal frailty model has 2 independent compound Poisson-distributed frailties and gives a significant improvement in fit over a unimodal frailty model. Applying the model to population-based cancer registry data worldwide, 2 biologically relevant estimates are derived, namely the proportion of susceptible individuals and the number of genetic and epigenetic events required for the tumor to develop. The results are critically compared and discussed in the context of existing knowledge of the epidemiology and pathogenesis of NPC.

Age-incidence curves of nasopharyngeal carcinoma worldwide: bimodality in low-risk populations and aetiologic implications.

The distinct geographic variation in the global incidence of nasopharyngeal carcinoma reflects a complex etiology involving viral, environmental, and genetic components. The high to intermediate rates observed in endemic areas contrast markedly with the uniformly low rates seen in much of the world. An interesting epidemiologic observation is the early peak in age-incidence curves observed in certain geographically disparate populations, suggestive of distinct causal entities and the possible exhaustion of susceptible individuals from the population at a certain age. The aim of this study was to systematically evaluate the age-incidence profiles of NPC worldwide on partitioning populations according to level of risk, in an effort to provide clues about the importance of early-in-life factors and genetic susceptibility. Using data from 23 high-quality population-based cancer registries for the period 1983-1997, a key finding was the consistent pattern of bimodality that emerged across low-risk populations, irrespective of geographic location. Continual increases in NPC risk by age up to a first peak in late adolescence/early adulthood (ages 15-24 years) were observed, followed by a second peak later in life (ages 65-79 years). No such early peak in NPC incidence by age group was evident among the high-risk populations studied. These findings are discussed according to existing lines of biological and epidemiologic evidence related to level of population risk, age at diagnosis, and histologic subtype. A modified model for NPC tumor development is proposed on the basis of these observations.

Exploring similarities and differences in hospital adverse event rates between Norway and Sweden using Global Trigger Tool.

OBJECTIVES: In this paper, we explore similarities and differences in hospital adverse event (AE) rates between Norway and Sweden by reviewing medical records with the Global Trigger Tool (GTT). DESIGN: All acute care hospitals in both countries performed medical record reviews, except one in Norway. Records were randomly selected from all eligible admissions in 2013. Eligible admissions were patients 18 years of age or older, undergoing care with an in-hospital stay of at least 24 hours, excluding psychiatric and care and rehabilitation. Reviews were done according to GTT methodology. SETTING: Similar contexts for healthcare and similar socioeconomic and demographic characteristics have inspired the Nordic countries to exchange experiences from measuring and monitoring quality and patient safety in healthcare. The co-operation has promoted the use of GTT to monitor national and local rates of AEs in hospital care. PARTICIPANTS: 10 986 medical records were reviewed in Norway and 19 141 medical records in Sweden. RESULTS: No significant difference between overall AE rates was found between the two countries. The rate was 13.0% (95% CI 11.7% to 14.3%) in Norway and 14.4% (95% CI 12.6% to 16.3%) in Sweden. There were significantly higher AE rates of surgical complications in Norwegian hospitals compared with Swedish hospitals. Swedish hospitals had significantly higher rates of pressure ulcers, falls and 'other' AEs. Among more severe AEs, Norwegian hospitals had significantly higher rates of surgical complications than Swedish hospitals. Swedish hospitals had significantly higher rates of postpartum AEs. CONCLUSIONS: The level of patient safety in acute care hospitals, as assessed by GTT, was essentially the same in both countries. The differences between the countries in the rates of several types of AEs provide new incentives for Norwegian and Swedish governing bodies to address patient safety issues.

Monitoring adverse events in Norwegian hospitals from 2010 to 2013.

OBJECTIVES: To describe how adverse event (AE) rates were monitored and estimated nationally across all Norwegian hospitals from 2010 to 2013, and how they developed during the monitoring period. Monitoring was based on medical record review with Global Trigger Tool (GTT). SETTING: All publicly and privately owned hospitals were mandated to review randomly selected medical records to monitor AE rates. The initiative was part of the Norwegian patient safety campaign, launched by the Norwegian Ministry of Health and Care Services. It started in January 2011 and lasted until December 2013. 2010 was the baseline for the review. One of the main aims of the campaign was to reduce patient harm. METHOD: To standardise the medical record reviews in all hospitals, GTT was chosen as a standard method. GTT teams from all hospitals reviewed 40,851 medical records randomly selected from 2,249,957 discharges from 2010 to 2013. Data were plotted in time series for local measurement and national AE rates were estimated, plotted and monitored. RESULTS: AE rates were estimated and published nationally from 2010 to 2013. Estimated AE rates in severity categories E-I decreased significantly from 16.1% in 2011 to 13.0% in 2013 (-3.1% (95% CI -5.2% to -1.1%)). CONCLUSIONS: Monitoring estimated AE rates emerges as a potential element in national systems for patient safety. Estimated AE rates in the category of least severity decreased significantly during the first 2 years of the monitoring.

Frailty modeling of the bimodal age-incidence of Hodgkin lymphoma in the Nordic countries.

BACKGROUND: The bimodality of the age-incidence curve of Hodgkin lymphoma (HL) has been ascribed to the existence of subgroups with distinct etiologies. Frailty models can be usefully applied to age-incidence curves of cancer to aid the understanding of biological phenomena in these instances. The models imply that for a given disease, a minority of individuals are at high risk, compared with the low-risk majority. METHODS: Frailty modeling is applied to interpret HL incidence on the basis of population-based cancer registry data from the five Nordic countries for the period 1993 to 2007. There were a total of 8,045 incident cases and 362,843,875 person-years at risk in the study period. RESULTS: A bimodal frailty analysis provides a reasonable fit to the age-incidence curves, employing 2 prototype models, which differ by having the sex covariate included in the frailty component (model 1) or in the baseline Weibull hazard (model 2). Model 2 seemed to fit better with our current understanding of HL than model 1 for the male-to-female ratio, number of rate-limiting steps in the carcinogenic process, and proportion of susceptibles; whereas model 1 performed better related to the heterogeneity in HL among elderly males. CONCLUSION: The present analysis shows that HL age-incidence data are consistent with a bimodal frailty model, indicating that heterogeneity in cancer susceptibility may give rise to bimodality at the population level, although the individual risk remains simple and monotonically increasing by age. IMPACT: Frailty modeling adds to the existing body of knowledge on the heterogeneity in risk of acquiring HL.